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Anti-CD20 Therapies in Drug-Naive Patients With Primary Progressive Multiple Sclerosis: A Multicenter Real-Life

Marion Hay1, Fabien Rollot1, Romain Casey1

  • 1From the Neurology Department (M.H., A.K., G.E., E.L.P., L. Michel), Rennes University Hospital; Clinical Neuroscience Centre (M.H., A.K., G.E., E.L.P., L. Michel), CIC_P1414 INSERM, Rennes, University Hospital, Rennes University; Université Claude Bernard Lyon 1 (F.R., R.C., S.V.), Université de Lyon; Service de Neurologie, Sclérose en Plaques, Pathologies de la Myéline et Neuro-inflammation (F.R., R.C., S.V.), Hospices Civils de Lyon, Bron; Observatoire Français de la Sclérose en Plaques (F.R., R.C., S.V.), Centre de Recherche en Neurosciences de Lyon, INSERM 1028 et CNRS UMR 5292; EUGENE DEVIC EDMUS Foundation Against Multiple Sclerosis, state-approved foundation (F.R., R.C., S.V.), Bron; Department of Neurology (G.M.), Nancy University Hospital; Université de Lorraine (G.M.), Inserm, INSPIIRE, Nancy; MS Unit (P.L.), CHU de Montpellier; University of Montpellier (MUSE) (P.L.); Department of Neurology and Clinical Investigation Center (J.D.S.), CHU de Strasbourg, CIC 1434, INSERM 1434; Service de Neurologie (D.-A.L.), CHU Nantes, Nantes Université, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, CIC INSERM 1413; Department of Neurology (C.P.), Fondation Rotschild, Paris; Department of Neurology (T.M.), CHU de Dijon, EA4184; Department of Neurology (E.T.), Nimes University Hospital; IGF (E.T.), University of Montpellier, CNRS, INSERM; CHU de Caen (G.D.), MS Expert Centre, Department of Neurology, Normandy University, Caen; Neurology (C.L.-F.), UR2CA_URRIS, Centre Hospitalier Universitaire Pasteur2, Université Nice Côte d'Azur, Nice; Department of Neurology (J.C.), CHU de Toulouse, CRC-SEP; Université Toulouse III (J.C.), Infinity, INSERM UMR1291-CNRS UMR5051; Service de Neurologie (E.B.), CHU de Besançon; Sorbonne Universités (B.S.), Paris Brain Institute, ICM, Inserm UMR S 1127, CNRS UMR 7225, and Department of Neurology, AP-HP, Hôpital de la Pitié Salpêtrière; CHU Clermont-Ferrand (P.C.), CRC SEP Auvergne, Department of Neurology, and INSERM NeuroDol U1107; Département de Neurologie (E.M.), Hôpital Pitié-Salpêtrière, APHP; Centre de Ressources et de Compétences SEP Paris (E.M.); Departement of Neurology (O.H.), Centre de Ressource et Compétences SEP IDF Ouest, Hôpital de Poissy; CHU Lille (H.Z.), CRCSEP Lille, Univ Lille, U1172; Department of Neurology (A.R.), University Hospital of Bordeaux; Neurocentre Magendie (A.R.), Bordeaux University, INSERM U1215; Department of Neurology (O.C.), CHU Grenoble Alpes, Neurology MS Clinic Grenoble, Grenoble Alpes University Hospital, La Tronche; Department of Neurology (S.M.), CHU de Reims, CRC-SEP; Department of Neurology (A.A.-K.), CHU d'Amiens; Departement of Neurology (B.B.), CHU de Rouen; Service de Neurologie (J.P.), Pôle de Neurosciences Cliniques, APHM, Hôpital de la Timone, Aix Marseille Univ; Department of Neurology (L. Magy), Hôpital Dupuytren, CHU de Limoges; Department of Neurology (J.-P.N.), Hôpital Jean Bernard, CHU La Milétrie, Poitiers; Department of Neurology (J.-P.C.), Hôpital Nord, CHU de Saint-Étienne; CRC SEP and Department of Neurology (I.D.), Hôpital Bretonneau, CHU de Tours; Department of Neurology (A.W.), Hôpital Henri Mondor, APHP, Créteil; Department of Neurology (M.T.), Hôpital Foch, Suresnes; Department of Neurology (C.L.), CHU Bicêtre; and Department of Neurology (K.H.), Hôpital Pierre Delafontaine, Centre Hospitalier de Saint-Denis, France.

Neurology
|September 25, 2024
PubMed
Summary

Anti-CD20 therapies did not significantly delay disability progression in primary progressive multiple sclerosis (PPMS) patients compared to untreated individuals. Further evaluation is needed to determine the optimal risk/benefit ratio for these treatments in PPMS.

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Area of Science:

  • Neurology
  • Immunology

Background:

  • Primary progressive multiple sclerosis (PPMS) is a debilitating neurological condition.
  • Anti-CD20 therapies have shown varied efficacy in MS, with ocrelizumab succeeding where rituximab failed in disability progression.
  • Evaluating anti-CD20 therapies in PPMS is crucial for treatment optimization.

Purpose of the Study:

  • To compare confirmed disability progression (CDP) in PPMS patients treated with anti-CD20 therapies versus a weighted untreated cohort.
  • To analyze secondary outcomes including relapse rates, MRI activity, risk factors for CDP, and serious infection incidence.

Main Methods:

  • Retrospective study using the French MS registry (2016-2021).
  • Inclusion of PPMS patients (Expanded Disability Status Scale ≤6.5) treated or untreated with anti-CD20 therapies.
  • Inverse probability of treatment weighting (IPTW) applied to compare outcomes, including time to CDP, relapse, MRI activity, and infection rates.

Main Results:

  • No significant difference in time to first CDP between treated and untreated PPMS patients (HR 1.13, p=0.2113).
  • A nonsignificant trend towards fewer relapses in the treated group (HR 0.83, p=0.0809).
  • Higher incidence of serious infections in the treated group (6.67 per 100 person-years vs. 2.67).

Conclusions:

  • Anti-CD20 therapy did not demonstrate superiority over no therapy in delaying CDP in previously untreated PPMS patients.
  • The study, primarily including rituximab-treated patients, highlights the need for continuous risk/benefit assessment.
  • Class III evidence suggests current anti-CD20 therapy is not superior to no therapy for delaying CDP in PPMS.